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CYP2D6 Gene

protein-coding   GIFtS: 74
GCID: GC22M042522

Cytochrome P450, Family 2, Subfamily D, Polypeptide 6

(Previous names: cytochrome P450, subfamily IID (debrisoquine, sparteine,...)
(Previous symbols: CYP2DL1, CYP2D7P2, CYP2D7BP, CYP2D8P2, CYP2D7AP)
Microbiology & Infectious Diseases Congress
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at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Cytochrome P450, Family 2, Subfamily D, Polypeptide 61 2     CYPIID62 3
CYP2DL11 2 3     EC 1.14.14.13 8
CYP2D7AP1 2     CPD62 5
CYP2D7BP1 2     P450DB12 5
CYP2D7P21 2     CYP2D2
CYP2D8P21 2     P450-DB12
Cytochrome P450, Family 2, Subfamily D, Polypeptide 7 Pseudogene 21 2     P450C2D2
Cytochrome P450, Family 2, Subfamily D, Polypeptide 8 Pseudogene 21 2     Cytochrome P450 2D62
Cytochrome P450, Subfamily II (Debrisoquine, Sparteine, Etc.,
-Metabolising), Polypeptide 7 Pseudogene 21 2
     Cytochrome P450, Subfamily IID (Debrisoquine, Sparteine, Etc.,
-Metabolizing)-Like 12
Cytochrome P450, Subfamily IID (Debrisoquine, Sparteine, Etc.,
-Metabolising), Polypeptide 8 Pseudogene 21 2
     Flavoprotein-Linked Monooxygenase2
Cytochrome P450, Subfamily IID (Debrisoquine, Sparteine, Etc.,
-Metabolizing), Polypeptide 61 2
     Microsomal Monooxygenase2
Cytochrome P450-DB12 3     Xenobiotic Monooxygenase2
Debrisoquine 4-Hydroxylase2 3     

External Ids:    HGNC: 26251   Entrez Gene: 15652   Ensembl: ENSG000001001977   OMIM: 1240305   UniProtKB: P106353   

Export aliases for CYP2D6 gene to outside databases

Previous GC identifers: GC22U990011 GC22M039139 GC22M040766 GC22M040768 GC22M040769 GC22M040848 GC22M040849 GC22M040852 GC22M025488


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for CYP2D6 Gene:
This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are
monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids
and other lipids. This protein localizes to the endoplasmic reticulum and is known to metabolize as many as 20%
of commonly prescribed drugs. Its substrates include debrisoquine, an adrenergic-blocking drug; sparteine and
propafenone, both anti-arrythmic drugs; and amitryptiline, an anti-depressant. The gene is highly polymorphic in
the population; certain alleles result in the poor metabolizer phenotype, characterized by a decreased ability to
metabolize the enzyme's substrates. The gene is located near two cytochrome P450 pseudogenes on chromosome
22q13.1. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.
(provided by RefSeq, Jul 2008)

GeneCards Summary for CYP2D6 Gene:
CYP2D6 (cytochrome P450, family 2, subfamily D, polypeptide 6) is a protein-coding gene. Diseases associated with CYP2D6 include debrisoquine sensitivity, and codeine sensitivity. GO annotations related to this gene include electron carrier activity and heme binding. An important paralog of this gene is CYP2W1.

UniProtKB/Swiss-Prot: CP2D6_HUMAN, P10635
Function: Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is
involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic
antidepressants

Gene Wiki entry for CYP2D6 Gene

PharmGKB "VIP" summary for CYP2D6


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000022.11  NT_011520.13  NC_018933.2  NT_187682.1  
Regulatory elements:
   Regulatory transcription factor binding sites in the CYP2D6 gene promoter:
         PPAR-gamma1   PPAR-gamma2   NF-kappaB1   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 4): CYP2D6 promoter sequence
   Search Chromatin IP Primers for CYP2D6

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat CYP2D6


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 22q13.1   Ensembl cytogenetic band:  22q13.2   HGNC cytogenetic band: 22q13.1

CYP2D6 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
CYP2D6 gene location

GeneLoc information about chromosome 22         GeneLoc Exon Structure

GeneLoc location for GC22M042522:  view genomic region     (about GC identifiers)

Start:
42,522,501 bp from pter      End:
42,526,908 bp from pter
Size:
4,408 bases      Orientation:
minus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: CP2D6_HUMAN, P10635 (See protein sequence)
Recommended Name: Cytochrome P450 2D6  
Size: 497 amino acids; 55769 Da
Cofactor: Heme group
4 PDB 3D structures from and Proteopedia for CYP2D6:
2F9Q (3D)        3QM4 (3D)        3TBG (3D)        3TDA (3D)    
Secondary accessions: Q16752 Q2XND6 Q2XND7 Q2XNE0 Q6B012 Q6NXU8
Alternative splicing: 2 isoforms:  P10635-1   P10635-2   (No experimental confirmation available)

Explore the universe of human proteins at neXtProt for CYP2D6: NX_P10635

Explore proteomics data for CYP2D6 at MOPED

Post-translational modifications: 

  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus
  • Selected DME Specific Peptides for CYP2D6 (P10635) (see all 20)
     VTTSTTL  EAFLPFS  LSSVLKD  NLSSVLK 


    See CYP2D6 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (2 alternative transcripts): 
    NP_000097.3  NP_001020332.2  

    ENSEMBL proteins: 
     ENSP00000353241   ENSP00000353820   ENSP00000351927   ENSP00000374620  
    Reactome Protein details: P10635

    CYP2D6 Human Recombinant Protein Products:

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    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    CYP: Cytochrome P450s

    IUPHAR Guide to PHARMACOLOGY protein family classification: CYP2D6
    CYP2 family

    4 InterPro protein domains:
     IPR001128 Cyt_P450
     IPR017972 Cyt_P450_CS
     IPR002401 Cyt_P450_E_grp-I
     IPR008069 Cyt_P450_E_grp-I_CYP2D-like

    Graphical View of Domain Structure for InterPro Entry P10635

    ProtoNet protein and cluster: P10635

    2 Blocks protein domains:
    IPB002401 E-class P450 group I signature
    IPB008069 CYP2D P450 family signature


    UniProtKB/Swiss-Prot: CP2D6_HUMAN, P10635
    Similarity: Belongs to the cytochrome P450 family


    CYP2D6 for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: CP2D6_HUMAN, P10635
    Function: Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is
    involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic
    antidepressants
    Catalytic activity: RH + reduced flavoprotein + O(2) = ROH + oxidized flavoprotein + H(2)O
    Induction: By pregnancy

         Enzyme Number (IUBMB): EC 1.14.14.11 2

         Gene Ontology (GO): Selected molecular function terms (see all 8):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004497monooxygenase activity IDA15327587
    GO:0005506iron ion binding IEA--
    GO:0008144drug binding IDA19448135
    GO:0016491oxidoreductase activity IDA15039299
    GO:0016705oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen ----
         
    CYP2D6 for ontologies           About GeneDecksing


    Phenotypes:
         2 GenomeRNAi human phenotypes for CYP2D6:
     Increased gamma-H2AX phosphory  Synthetic lethal with c-Myc af 

    Animal Models:
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    hsa-mir-26b-5p (MIRT029578)

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    Browse SwitchGear 3'UTR luciferase reporter plasmids
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    GenScript: all cDNA clones in your preferred vector (see all 2): CYP2D6 (NM_000106)
    Sino Biological Human cDNA Clone for CYP2D6
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for CYP2D6
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat CYP2D6

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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for CYP2D6


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    CP2D6_HUMAN, P10635: Endoplasmic reticulum membrane; Peripheral membrane protein. Microsome membrane; Peripheral
    membrane protein
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    endoplasmic reticulum5
    mitochondrion4
    cytosol2
    nucleus2
    extracellular1
    lysosome1
    peroxisome1
    plasma membrane1

    Gene Ontology (GO): 3 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005739mitochondrion IDA19438707
    GO:0005783endoplasmic reticulum TAS19438707
    GO:0005789endoplasmic reticulum membrane TAS--

    CYP2D6 for ontologies           About GeneDecksing


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for CYP2D6 About   (see all 12)                                                                                              See pathways by source

    SuperPathContained pathways About
    1Biological oxidations
    Biological oxidations0.56
    Phenytoin Pathway, Pharmacokinetics0.00
    metapathway biotransformation0.42
    Tamoxifen metabolism0.00
    Benzodiazepine Pathway, Pharmacokinetics0.00
    Estradiol metabolism0.00
    Tamoxifen Pathway, Pharmacokinetics0.00
    Acetaminophen metabolism0.00
    2Cytochrome P450 - arranged by substrate type
    Cytochrome P450 - arranged by substrate type0.75
    Xenobiotics0.00
    Phase 1 - Functionalization of compounds0.75
    Miscellaneous substrates0.00
    cytochrome P4500.74
    Fatty Acid Omega Oxidation0.00
    Fatty acids0.00
    CYP2E1 reactions0.00
    3Chemical carcinogenesis
    Metabolism of xenobiotics by cytochrome P4500.71
    Celecoxib Pathway, Pharmacokinetics0.00
    Drug metabolism - cytochrome P4500.69
    4Codeine and Morphine Pathway, Pharmacokinetics
    Codeine and Morphine Pathway, Pharmacokinetics0.33
    Codeine and morphine metabolism0.00
    Tramadol Pharmacokinetics0.33
    5Venlafaxine Pathway, Pharmacokinetics
    Venlafaxine Pathway, Pharmacokinetics0.67
    Imipramine/Desipramine Pathway, Pharmacokinetics0.50
    Citalopram Pathway, Pharmacokinetics0.67
    Nevirapine Pathway, Pharmacokinetics0.50
    Fluoxetine Pathway, Pharmacokinetics0.57
    Clomipramine Pathway, Pharmacokinetics0.00

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways


    4 GeneGo (Thomson Reuters) Pathways for CYP2D6
        Estradiol metabolism
    NAD metabolism
    Retinol metabolism
    Acetaminophen metabolism

    5 BioSystems Pathways for CYP2D6
        cytochrome P450
    Codeine and morphine metabolism
    Tamoxifen metabolism
    metapathway biotransformation
    Fatty Acid Omega Oxidation


    4 Reactome Pathways for CYP2D6
        Miscellaneous substrates
    Fatty acids
    Xenobiotics
    CYP2E1 reactions

    Selected PharmGKB Pathways for CYP2D6 (see all 19)
        Acetaminophen Pathway, Pharmacokinetics
    Atorvastatin/Lovastatin/Simvastatin Pathway, Pharmacokinetics
    Benzodiazepine Pathway, Pharmacokinetics
    Celecoxib Pathway, Pharmacokinetics
    Citalopram Pathway, Pharmacokinetics

    3 Kegg Pathways  (Kegg details for CYP2D6):
        Metabolism of xenobiotics by cytochrome P450
    Drug metabolism - cytochrome P450
    Serotonergic synapse


    CYP2D6 for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Arrays including CYP2D6 (see all 6): 
              Nephrotoxicity in human mouse rat
              Cancer Drug Resistance in human mouse rat
              Drug Metabolism: Phase I Enzymes in human mouse rat
              Cellular Stress Responses in human mouse rat
              Molecular Toxicology PathwayFinder 384HT in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for CYP2D6

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for CYP2D6 (P106353 ENSP000003538204) via UniProtKB, MINT, STRING, and/or I2D (see all 36)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    MAGEB4O154813I2D: score=1 
    SAT1P216733I2D: score=1 
    CYP2C18ENSP000002859794STRING: ENSP00000285979
    CYP2C19ENSP000003603724STRING: ENSP00000360372
    CYP2C8ENSP000003603174STRING: ENSP00000360317
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 15):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006805xenobiotic metabolic process TAS19438707
    GO:0008202steroid metabolic process IMP18356043
    GO:0009804coumarin metabolic process IDA19438707
    GO:0009820alkaloid metabolic process IDA19651758
    GO:0009822alkaloid catabolic process IDA15039299

    CYP2D6 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for CYP2D6 (CP2D6)

    Selected HMDB Compounds for CYP2D6 (see all 70)    About this table
    CompoundSynonyms CAS #PubMed Ids
    10-HETE10-hydroxyeicosa-all-cis-5,8,11,14-tetraenoate (see all 2)167697-52-1--
    11,12,15-THETA11,12,15-Trihydroxyicosatrienoic acid (see all 5)----
    11,12-Epoxyeicosatrienoic acid10-(3-(2-octenyl)oxiranyl)-5,8-Decadienoic acid (see all 15)81276-02-0--
    11,14,15-THETA(5Z,8Z,12E)-11,14,15-Trihydroxyeicosa-5,8,12-trienoic acid (see all 8)----
    11H-14,15-EETA14,15-Ep-11-HETrE (see all 11)219535-29-2--
    11beta-Hydroxytestosterone11beta,17beta-dihydroxyandrost-4-en-3-one 1816-85-9--
    12,13-EpOMEVernolic acid (see all 12)----
    13-HETE13-hydroxy-5Z,8Z,11Z,14Z-eicosatetraenoate (see all 2)151910-72-4--
    14,15-Epoxy-5,8,11-eicosatrienoic acid(5Z,8Z,11Z)-14,15-Epoxyicosa-5.8.11-trienoic acid (see all 11)81276-03-1--
    15(S)-HPETE(5Z,8Z,11Z,13E)-(15S)-15-Hydroperoxyicosa-5,8,11,13-tetraenoate (see all 8)70981-96-3--

    Selected DrugBank Compounds for CYP2D6 (see all 305)    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    TamoxifenICI-46474 (see all 3)10540-29-1enzymesubstrate inhibitor12124303 1500011 15159443 1500055 20425602 19934256 19515014
    AmitriptylineAmitriprolidine (see all 5)50-48-6enzymesubstrate inhibitor11259560 9131945 8968657 18359012 19934256 19515014
    Fluoxetine-- 54910-89-3enzymesubstrate inhibitor18537577 10774624 16910628 8968657 19934256 19515014
    PerphenazineChlorperphenazine (see all 8)58-39-9enzymesubstrate inhibitor9333110 16910628 10688273 19934256 9616188 8689810
    Risperidonerisperdone (see all 3)106266-06-2enzymesubstrate inhibitor19902987 19817501 10048600 11560868 19934256 19910717
    Chlorpromazine-- 50-53-3enzymesubstrate inhibitor16910628 10688273 19934256 10901285 11996015
    DextromethorphanD-Methorphan (see all 20)125-71-3enzymesubstrate inhibitor19817501 12401364 11602530 19934256 19515014
    Doxepin-- 1668-19-5enzymesubstrate inhibitor15168101 11037801 12360109 19934256 15520506
    Nortriptyline-- 72-69-5enzymesubstrate inhibitor10354960 18359012 19934256 9193876 19515014
    SertralineSertralina [Spanish] (see all 3)79617-96-2enzymesubstrate inhibitor12143142 16910628 15547048 8968657 19934256

    Selected Novoseek inferred chemical compound relationships for CYP2D6 gene (see all 156)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    debrisoquine 96.9 338 10752638 (5), 11723233 (5), 9316857 (4), 1978565 (3) (see all 99)
    bufuralol 93.4 56 15183128 (3), 16563352 (3), 11266079 (3), 12167561 (2) (see all 36)
    sparteine 91.2 56 8351162 (3), 1531950 (2), 10634134 (2), 11549206 (2) (see all 41)
    quinidine 88.3 116 10702886 (6), 7575645 (5), 7593709 (5), 8100167 (3) (see all 64)
    dextrorphan 84.7 40 18543297 (5), 7593709 (3), 10942192 (3), 10774635 (2) (see all 15)
    3-methoxymorphinan 83.7 8 8873685 (2), 10942192 (2), 7826826 (1), 10774635 (1)
    furafylline 81.5 1 9431831 (1)
    mephenytoin 81.3 28 10424320 (2), 8737964 (2), 10774635 (2), 18979093 (1) (see all 19)
    bunitrolol 80.8 10 7663534 (3), 15618721 (1), 7951142 (1), 9914647 (1) (see all 5)
    1'-hydroxybufuralol 78 1 12167561 (1)

    Selected PharmGKB related drug/compound annotations for CYP2D6 gene (see all 49)    About this table
    Drug/compound PharmGKB Annotation
    acetaminophen
    amitriptyline
    aripiprazole
    atomoxetine
    carvedilol
    cevimeline
    citalopram
    clomipramine  CA  
    clozapine
    codeine



    CYP2D6 for compounds           About GeneDecksing



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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    REFSEQ mRNAs for CYP2D6 gene (2 alternative transcripts): 
    NM_000106.5  NM_001025161.2  

    Unigene Clusters for CYP2D6:

    Cytochrome P450, family 2, subfamily D, polypeptide 6
    Hs.333497  [show with all ESTs], Hs.648256  [show with all ESTs]
    Unigene Representative Sequences: AY220845, AB209492
    5 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000360124(uc010gyu.3) ENST00000360608(uc003bce.3 uc003bcf.3)
    ENST00000488442 ENST00000359033 ENST00000389970
    Congresses - knowledge worth sharing:
    European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 10 - 13 May 2014

    miRNA
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    OriGene clones in human, mouse for CYP2D6 (see all 12)
    OriGene ORF clones in mouse, rat for CYP2D6
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector (see all 2): CYP2D6 (NM_000106)
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for CYP2D6
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat CYP2D6
    Primer
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    OriGene qPCR primer pairs and template standards for CYP2D6
    OriGene qSTAR qPCR primer pairs in human, mouse for CYP2D6
    Pre-validated RT2 qPCR Primer Assay in human, mouse, rat CYP2D6
      QuantiTect SYBR Green Assays in human, mouse, rat CYP2D6
      QuantiFast Probe-based Assays in human, mouse, rat CYP2D6

    Additional mRNA sequence: 

    AB209492.1 AK308211.1 AK309600.1 AY663390.1 BC066877.1 BC067432.1 BC075023.2 BC075024.2 
    BC106757.1 BC106758.1 BC126857.1 BC126858.1 CR456430.1 M20403.1 M24499.1 X08006.1 
    X16865.1 

    19 DOTS entries:

    DT.456039  DT.75148866  DT.101983084  DT.100861542  DT.91734821  DT.120667070  DT.95345407  DT.99937608 
    DT.97806204  DT.100797188  DT.120667041  DT.120667088  DT.91742565  DT.100797187  DT.40200615  DT.100797190 
    DT.100797191  DT.120667093  DT.91690659 

    Selected AceView cDNA sequences (see all 107):

    CR456430 BC067432 CB137789 AV645915 CB122244 AI581683 CB134922 NM_000106 
    CB144729 BC066877 AV689088 BX422592 AV651120 BV188663 CB142772 M24499 
    X07618 CF271948 CB162434 BX430832 CB124853 BC075024 AV693266 CB139124 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for CYP2D6 (see all 13)    About this scheme

    ExUns: 1 ^ 2a · 2b ^ 3a · 3b · 3c ^ 4 ^ 5a · 5b ^ 6 ^ 7a · 7b ^ 8 ^ 9a · 9b · 9c ^ 10 ^ 11 ^ 12 ^ 13a · 13b · 13c ^ 14 ^ 15 ^ 16 ^ 17a ·
    SP1:                                                                                                                    -                                       
    SP2:                                                                                                                    -                 -                     
    SP3:                                                                                                                                                            
    SP4:                                                                                                                                      -                 -   
    SP5:                                                              -                                                                                             

    ExUns: 17b ^ 18 ^ 19 ^ 20a · 20b ^ 21
    SP1:                                    
    SP2:                                    
    SP3:                                    
    SP4:                                    
    SP5:                                    


    ECgene alternative splicing isoforms for CYP2D6

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    CYP2D6 expression in normal human tissues (normalized intensities)      CYP2D6 embryonic expression: see
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: --
    CYP2D6 Expression
    About this image


    CYP2D6 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 4) fully expand
     
     Liver (Hepatobiliary System)
             Mature Hepatocytes Liver Lobule
     
     Endothelium (Cardiovascular System)
             Endothelial Cells Blood Brain Barrier
     
     Brain (Nervous System)
             Endothelial Cells Blood Brain Barrier
     
     Amnion (Extraembryonic Tissues)
             Amniotic Epithelial Cells Amniotic Membrane
    CYP2D6 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    CYP2D6 Protein Expression

    SOURCE GeneReport for Unigene clusters: Hs.333497 Hs.648256
        Pathway & Disease-focused RT2 Profiler PCR Arrays including CYP2D6 (see all 6): 
              Nephrotoxicity in human mouse rat
              Cancer Drug Resistance in human mouse rat
              Drug Metabolism: Phase I Enzymes in human mouse rat
              Cellular Stress Responses in human mouse rat
              Molecular Toxicology PathwayFinder 384HT in human mouse rat

    Primer
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    QuantiFast Probe-based Assays in human, mouse, rat CYP2D6
    In Situ
    Assay Products:
     

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for CYP2D6

    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of chordates.

    Orthologs for CYP2D6 gene from Selected species (see all 12)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Cyp2d225 cytochrome P450, family 2, subfamily d, polypeptide 22 less   --   15 (38.57 cM) 82370528 
    chicken
    (Gallus gallus)
    Aves CYP2D61 cytochrome P450, family 2, subfamily D, polypeptide 6 less 60.03(n)
    56.26(a)
      417981  NM_001195557.1  NP_001182486.1 
    lizard
    (Anolis carolinensis)
    Reptilia CYP2D66
    cytochrome P450, family 2, subfamily D, polypeptid...
    48(a)
    1 ↔ 1
    5(27228365-27244663)
    tropical clawed frog
    (Xenopus tropicalis)
    Amphibia cyp2d61 cytochrome P450, family 2, subfamily D, polypeptide 6 less 58.32(n)
    54.62(a)
      548436  NM_001015719.1  NP_001015719.1 
    zebrafish
    (Danio rerio)
    Actinopterygii cyp2aa126
    cyp2aa116
    (see all 9)
    cytochrome P450, family 2, subfamily AA, polypepti...
    cytochrome P450, family 2, subfamily AA, polypepti...
    (see all 9)
    41(a)
    40(a)
    (see all 9)
    many ↔ many
    many ↔ many
    (see all 9)
    23(43010133-43024136) ENSDARG00000091156
    23(42958102-42969656) ENSDARG00000041418


    ENSEMBL Gene Tree for CYP2D6 (if available)
    TreeFam Gene Tree for CYP2D6 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for CYP2D6 gene
    CYP2W12  CYP2C82  CYP2A62  CYP2F12  CYP2A72  CYP2B62  CYP2C192  CYP2R12  
    CYP2J22  CYP2U12  CYP2S12  CYP2E12  CYP2C92  CYP2C182  CYP2A132  
    Selected SIMAP similar genes for CYP2D6 using alignment to 39 protein entries:     CP2D6_HUMAN (see all proteins) (see all similar genes):
    CYP2D7P1    CYP2G1P    CYP2R1    CYP2J2    CYP2U1    CYP2B6
    CYP2A6    CYP2A13    CYP2A7    CYP2E1    CYP 2C    CYP2B
    CYP2C19    CYP2B7    CYP2C9    CYP2A6V2    CYP2C8    CYP2S1

    CYP2D6 for paralogs           About GeneDecksing


    2 Pseudogenes.org Pseudogenes for CYP2D6
    PGOHUM00000259332 PGOHUM00000237892


    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Polymorphic Variants from UniProtKB/Swiss-Prot
    CP2D6_HUMAN, P10635: Genetic variations in CYP2D6 are the cause of poor drug metabolism CYP2D6-related [MIM:608902]. The
    CYP2D6 gene is highly polymorphic. CYP2D6 activity ranges widely within a population comprising ultrarapid (UM),
    extensive (EM), intermediate (IM) and poor (PM) metabolizer phenotypes. UM and PM are those most at risk for
    treatment failure or dose-dependent drug toxicity, respectively. Of the Caucasian populations of Europe and North
    America, 5%-10% are of the PM phenotype and are unable to metabolize the antihypersensitive drug debrisoquine and
    numerous other drugs
    CP2D6_HUMAN, P10635: Allele CYP2D6*7 was also known as CYP2D6E, allele CYP2D6*9 as CYP2D6C, allele CYP2D6*10 as CYP2D6J,
    allele CYP2D6*17 as CYP2D6Z
    CP2D6_HUMAN, P10635: Isozymes CYP2D6.45 (Lys-155, Cys-296 and Thr-486) and CYP2D6.46 (His-26, Lys-155, Cys-296 and
    Thr-486) are functional


    Selected SNPs for CYP2D6 (see all 448)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 22 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs50308651,2
    C,Fpathogenic142525035(+) CCCACA/C/TGGAGT 3 G * stg1 int14NS NA 102
    rs10658521,2,,4
    C,Fpathogenic142526694(-) GCTACC/TCACCA 4 P S mis1 ese313Minor allele frequency- T:0.21NS WA NA EA EU 5579
    rs11358401,2,,4
    C,Funtested142522613(-) GGTGAC/GCCCAT 4 T S mis1 ese313Minor allele frequency- G:0.39NS NA WA CSA EA EU 5627
    rs1410094911,2
    Cuntested142523633(+) GGACAC/GGGCCT 4 P R mis11Minor allele frequency- T:0.00NA 4534
    rs2676082891,2
    Cuntested142525733(+) ACCGCC/TGCTTG 2 -- int10--------
    rs2676082821,2
    Cuntested142525946(+) AAGCCA/GGGATC 2 -- int10--------
    rs2676082751,2
    Cuntested142526051(+) ATCCT-/GGGGCG 2 -- int10--------
    rs40782481,2
    C,F--42522027(+) GGGAAC/TGTTCT 2 -- int16Minor allele frequency- T:0.18NS WA CSA 218
    rs793473911,2
    C,F--42522028(-) CAGAAC/TGTTCC 2 -- int13Minor allele frequency- T:0.01NS 96
    rs350286221,2
    C,F--42522074(+) CTGGCC/ATATAG 2 -- int112Minor allele frequency- A:0.38NA NS WA EA 466

    HapMap Linkage Disequilibrium report for CYP2D6 (42522501 - 42526908 bp)

    Structural Variations
         Database of Genomic Variants (DGV) Selected variations for CYP2D6 (see all 17):    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2724275CNV Deletion23290073
    dgv780e201CNV Deletion23290073
    nsv436350CNV Deletion17901297
    esv2171396CNV Deletion18987734
    nsv508737CNV Insertion20534489
    nsv3642CNV Insertion18451855
    nsv3641CNV Loss18451855
    nsv834210CNV Loss17160897
    nsv498989CNV Loss21111241
    nsv829243CNV Loss20364138

    The Human Cytochrome P450 Allele Nomenclature Database: CYP2D6 
    Human Gene Mutation Database (HGMD): CYP2D6
    Locus Specific Mutation Databases (LSDB): CYP2D6

    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing CYP2D6
    DNA2.0 Custom Variant and Variant Library Synthesis for CYP2D6

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 124030   
    OMIM disorders: 608902  
    Selected diseases for CYP2D6 (see all 142):    About MalaCards
    debrisoquine sensitivity    codeine sensitivity    cytochrome p450 2d6 variant    pseudobulbar affect
    neuroleptic malignant syndrome    autoimmune hepatitis    multiple chemical sensitivity    serotonin syndrome
    tardive dyskinesia    systolic heart failure    hypersomnia    hepatitis d
    drug-induced hepatitis    schizoaffective disorder    multiple system atrophy    gastroparesis
    addison's disease    substance abuse    spondylitis    laryngeal squamous cell carcinoma

    10 diseases from the University of Copenhagen DISEASES database for CYP2D6:
    Autoimmune hepatitis     Schizophrenia     Breast cancer     Neuroleptic malignant syndrome
    Parkinson's disease     Pain agnosia     Liver disease     Lung cancer
    Schizoaffective disorder     Hepatitis C

    CYP2D6 for disorders           About GeneDecksing


    Congresses - knowledge worth sharing:
    Alzheimer's & Parkinson's Diseases Congress (ADPD) 18 - 22 March 2015

    Selected Novoseek inferred disease relationships for CYP2D6 gene (see all 71)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    hepatitis autoimmune 71.3 35 16037945 (2), 9719237 (2), 15747502 (2), 10540193 (2) (see all 23)
    neuroleptic malignant syndrome 47 13 9323326 (4), 9892857 (1), 11204351 (1), 16048458 (1) (see all 6)
    parkinson disease 44 57 9189044 (4), 8627546 (2), 18300942 (2), 20364044 (2) (see all 33)
    genetic susceptibility 42 4 18300942 (1), 7581482 (1), 20225176 (1), 8035747 (1)
    hepatitis c chronic 35.6 11 9672171 (2), 10772926 (2), 8905121 (1), 9328334 (1) (see all 9)
    cancer recurrence 34.8 5 20439629 (2), 19690182 (1), 19244106 (1)
    schizophrenia 31.3 57 18034624 (5), 16478753 (4), 18520596 (3), 11702057 (3) (see all 22)
    lewy body disease 30.5 5 9316701 (1), 10534269 (1), 16337409 (1), 10071712 (1)
    breast cancer 26.4 59 20439629 (4), 18445827 (3), 18407954 (3), 18794105 (3) (see all 33)
    parkinsonism 25.6 7 9286632 (1), 8937349 (1), 9109653 (1), 8723226 (1) (see all 5)

    Genatlas disease: CYP2D6
    debrisoquine sensitivity (poor metabolizer,CYP2D6 mutant) including neuroleptic malignant syndrome,putative
    susceptibility gene for leukemia

    Genetic Association Database (GAD): CYP2D6
    Human Genome Epidemiology (HuGE) Navigator: CYP2D6 (571 documents)

    Export disorders for CYP2D6 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for CYP2D6 gene, integrated from 10 sources (see all 1718):
    (articles sorted by number of sources associating them with CYP2D6)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Impact of CYP2D6 genotype on steady-state serum concentrations of risperidone and 9-hydroxyrisperidone in patients using long-acting injectable risperidone. (PubMed id 19910717)1, 4, 7, 9 Hendset M....Hermann M. (J Clin Psychopharmacol 2009)
    2. A novel mutant variant of the CYP2D6 gene (CYP2D6*17) common in a black African population: association with diminished debrisoquine hydroxylase activity. (PubMed id 8971426)1, 2, 4, 9 Masimirembwa C....Ingelman-Sundberg M. (Br. J. Clin. Pharmacol. 1996)
    3. A missense mutation in exon 6 of the CYP2D6 gene leading to a histidine 324 to proline exchange is associated with the poor metabolizer phenotype of sparteine. (PubMed id 7845481)1, 2, 4, 9 Evert B.... Eichelbaum M. (Naunyn Schmiedebergs Arch. Pharmacol. 1994)
    4. Influence of CYP2D6 genotype on metoprolol plasma concentration and beta-adrenergic inhibition during long-term treatment: a comparison with bisoprolol. (PubMed id 16220080)1, 4, 7 Nozawa T....Inoue H. (J. Cardiovasc. Pharmacol. 2005)
    5. Contributions of CYP2D6, CYP2C9 and CYP2C19 to the biotransformation of E- and Z-doxepin in healthy volunteers. (PubMed id 12360109)1, 4, 7 Kirchheiner J....BrockmAPller J. (Pharmacogenetics 2002)
    6. Polymorphism of human cytochrome P450 2D6 and its clinical significance: part II. (PubMed id 19902987)1, 7, 9 Zhou S.F. (Clin Pharmacokinet 2009)
    7. Cytochrome P450 2D6 and homeobox 13/interleukin-17B receptor: combining inherited and tumor gene markers for prediction of tamoxifen resistance. (PubMed id 18794098)1, 4, 9 Goetz M.P....Ingle J.N. (Clin. Cancer Res. 2008)
    8. Allelic distributions of CYP2D6 gene copy number variation in the Eastern Han Chinese population. (PubMed id 17241532)1, 4, 9 Sheng H.H....Xiao H.S. (Acta Pharmacol. Sin. 2007)
    9. A study of genetic (CYP2D6 and ABCB1) and environmental (drug inhibitors and inducers) variables that may influence plasma risperidone levels. (PubMed id 17541883)1, 4, 9 Leon J.d....Diaz F.J. (Pharmacopsychiatry 2007)
    10. The impact of pharmacogenomics on postoperative nausea and vomiting: do CYP2D6 allele copy number and polymorphisms affect the success or failure of ondansetron prophylaxis? (PubMed id 15731591)1, 4, 9 Candiotti K.A....Andrews D. (Anesthesiology 2005)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 1565 HGNC: 2625 AceView: CYP2D6andCYP2D7P1andLOC440832 Ensembl:ENSG00000100197 euGenes: HUgn1565
    ECgene: CYP2D6 Kegg: 1565 H-InvDB: CYP2D6

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for CYP2D6 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for CYP2D6 Genetics and Cytogenetics in Oncology and Haematology
    Cytochrome P450 Allele Nomenclature Committeehttp://www.cypalleles.ki.se/cyp2d6.htm
    Wikipedia http://en.wikipedia.org/wiki/CYP2D6

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for CYP2D6 gene:
    Search GeneIP for patents involving CYP2D6

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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